Matthew Ware PAC HematologyOncology BMT Froedtert and the Medical College of Wisconsin Cancer Center Disclosures None Objectives Understand basic labs Interpreting myeloma labs Imaging and its role ID: 999609
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1. Multiple Myeloma and Understanding your LabsMatthew Ware PA-CHematology/Oncology, BMTFroedtert and the Medical College of Wisconsin Cancer Center
2. DisclosuresNone
3. ObjectivesUnderstand basic labsInterpreting myeloma labsImaging and its roleDiagnosing myeloma
4. Topics for DiscussionWhat is myelomaHematopoiesisMonoclonal proteins and detectionCytogeneticsCRABDiagnosingResponses
5. MyelomaWhat is Myeloma? Disorder of white blood cells called plasma cells, which produce antibodies (immunoglobulins)-Antibody is part of your immune system's defense
6. HematopoiesisHematopoiesis- formation of blood cells. Restricted to the skull, vertebrae, pelvis, and metaphyseal areas of long bones in adults [Mac]
7. White Blood Cells (Leukocytes)WBCs are involved in fighting infections and foreign invadersTwo major categoriesAgranulocytesGranulocytes
8. WBCs- AgranulocytesNo granules in their cytoplasm and one lobe nucleus. Also called mononuclear leukocytesTwo types: LymphocytesMonocytes
9. WBCs- Agranulocytes: LymphocytesLymphocytes include Natural killer (NK) cells- cytotoxic or lead to cell deathT cells- adaptive cytotoxic function B cells- antibody driver adaptive immunityThese are plasma cells
10. WBCs- Agranulocytes: MonocytesMonocyte is the largest type of leukocyte and can attack, eat foreign material and that presented to them by T cells
11. WBCs- GranulocytesGranules in their cytoplasm and differing shape of their nucleus also call polymorphonuclear leukocytes (PML or PMN)Three major categoriesNeutrophils are 40-70% of WBCs. Elevated with inflammation or infection and fight infectionEosinophils fight parasites and can be elevated in allergic reactionsBasophils seen in inflammatory responses, acute and chronic
12. Red Blood Cells (Erythrocytes) and PlateletsHemoglobin (Hb or Hgb)is the iron-containing oxygen-transport protein in the RBCs Oxygen and carbon dioxide exchange in the lungs and tissuesPlatelets- involved in clotting after a bleed. Fragments from megakaryocytes
13. Diagnosing MyelomaLab resultsCBC and chemistry panelProtein evaluation (blood and urine)Immunoglobulin (antibodies) levels- IgG, IgA, IgMImagingBone lesions: X-ray (bone survey), CT, MRI, PETPathologyBone marrow biopsy and cytogenetics
14. Monoclonal ProteinPresent in majority of patients and 97% have a monoclonal or M protein Made by non-functioning plasma cell seen in serum and/or 24 hour urine. Termed paraproteinTesting- serum protein electropheresis (SPEP) or urine protein electopheresis (UPEP)No detectable protein in 3% (non-secretory)
15. Monoclonal ProteinImmunofixation (IFE) identifies the heavy and light chain components Protein elecrophoresis (PEP) quantifies the protein
16. ImmunoglobulinIMF, 2018
17. Monoclonal ProteinIgG- 52%IgA- 21%Kappa or lambda chain only (Bence Jones)- 16%IgD- 2%Biclonal- 2%IgM- 0.5%Negative- 6.5%
18. Free Light Chains (FLC)Measures Kappa and Lambda not bound to heavy chains. Normal ratio Kappa:Lambda is 2:1 for intact proteins and 0.26 to 1.65 when measuring those unbound to heavy chains in the blood Ratio over 100, there was a 70-80% chance of end organ damage in 2 years
19. Serum ImmunoglobulinsIgG, IgA, IgMReduction in uninvolved immunoglobulins90% to have reduction in one70% to have both reduced
20. Bone Marrow BiopsyPercentage of plasma cells- Normal range is 1-2%Morphology- mature, immature, atypicalMature is better prognosisCan derive kappa/lambda ratio from here or serumCytogenetics- Chromosomal abnormalities
21. Bone Marrow BiopsyIMF, 2018
22. Bone Marrow- CytogeneticsChromosome abnormalitiesConventional karyotype is 20-30%-Number and appearance of chromosomes gains, loses of chromosomes or deletions. Seen in dividing cells (1-3% of the plasma cells)G, 2018
23. Bone Marrow- FISHFluorescent in situ hybridization (FISH)- Fluorescent labeled DNA sequences that find a complement on the plasma cells Detects changes regardless of plasma cells growthChromosome- Long (q) and short (p) arm make up a chromatid
24. Bone Marrow- FISHIMF, 2018
25. Cytogenetics and FISH
26. Presenting SymptomsCRABCalcium (elevated)Renal (kidney) FailureAnemiaBone Lesions
27. CRABCalcium (elevated)- HypercalcemiaResults from bone break downSymptoms of nausea, constipation, poor appetite, confusion, thirstSeen in 28% of patients on presentation
28. CRABRenal (kidney) Failure or DysfunctionCreatinine is a waste product from normal muscle breakdown, filtered by kidneys and excretedIncreased by monoclonal proteins and high calciumSymptoms of confusion, weakness, nausea, fatigue, fluid retention, decreased urine outputElevated creatinine in 48% on presentation
29. CRABAnemiaLower red blood cells (hemoglobin)Marrow replaced by cancer cellsPresent with fatigue, weakness, lightheadedness, slowed thinkingSeen in 73% patients on diagnosis
30. CRABBone LesionsPain, commonly seen in ribs and spinal cordBone breakdown can lead to fractures (broken bones), which release calcium into the bloodstream (hypercalcemia)Compression fracturesSeen in 58% on presentation
31. ImagingX-ray or bone surveyCTMRIPET
32. X-ray or Bone (skeletal) surveyThinning of bone or lytic lesions (holes in bone) and/or fracturesLimitation: 30% or more of trabecular (cancellous or spongy) bone must be missing to be seen on x-ray and 50-75% from lumbar vertebra before visibleAppearance may not change following therapyNot best for determining cause of pain Not sensitive for focal lesions in bone marrow
33. X-rayAC, 2018
34. CT (Computed [axial] Tomography)Cross sectional x-rayDetection in up to 25% of those with negative x-raySoft tissue masses seen compared to x-rayQuicker than x-rayNot as sensitive as MRI in detecting lesions outside bone marrowContrastMore expensive than x-ray
35. CTAC, 2018
36. MRI (Magnetic Resonance Imaging)Picks up bone marrow involvementPreferred for spinal cord assessment (compression)Osteoporosis vs vertebral fractures52% had normal x-rays Limitations: expensive, time consuming, implants (metal), pacemakers, claustrophobia, contrast and kidney function9 month lag time of active disease
37. MRIAC, 2018
38. PET (Positron Emission Tomography)Radiolabeled glucose, uptake taken by cancer cells (actively dividing), muscle and brainFDG- fluorodeoxyglucoseFind a mass where there is no bone lesionExtramedullary disease (Non-secretory)Three or more lesions poorer OS and PFSExpensiveInflammation Skull lesions missed due to FDG avidity of brainMedicare covers 1 PET scan May cover additional during relapse, non-secretory additional malignancy
39. PETAC, 2018
40. Additional LabsBeta-2 microglobulin- (B2M) is a protein on the cell surface of most cells. Shed into bloodstream. Commonly seen on B lymphocytes and tumor Total protein- albumin and globulin. M-protein increases blood globulinAlbumin- Most abundant protein in blood plasma LDH (Lactate dehydrogenase)- enzyme in almost every cell and involved in fueling cells. Seen when cells are rapidly dividing and dying
41. RISS (Revised International Staging System)Based on blood workAmount of albuminBeta-2 microglobulin LDHCytogenetics (bone marrow)3 stages
42. RISS- StagesStage IBeta-2 microglobulin < 3.5 mg/L AND Albumin is 3.5 g/dL or greater AND standard cytogenetics AND normal LDH levelsStage IINot stage I or IIIStage IIIBeta-2 microglobulin > 5.4 mg/L AND high risk cytogenetics AND/OR LDH high (2 times upper limit of normal)Median overall survival (OS) for patients with ISS stages I, II, and III were 62, 44, and 29 months, respectively.
43. Diagnostic Criteria
44. ResponsesIMWG, 2018